Role of proteoglycans in the organization of periurethral connective tissue in women with stress urynary incontinence

Objectives: Connective tissue consists of fibroblasts and extracellular matrix (ECM) with collagen and elastic fibers, glycoproteins and proteoglycans (PGs) and it is considered an important factor of the supportive structures of the genitourinary region. Since PGs are essential for the organization of the collagen fibrils in the ECM, we investigated the presence of two PGs, fibromodulin and lumican, and of collagen type I in the periurethral connective tissue from women with stress urinary incontinence (SUI), compared to asymptomatic controls. Methods: Thirty-two patients participated in the study and they were divided into four groups: premenopausal incontinents, premenopausal controls, postmenopausal incontinents and postmenopausal controls. All patients underwent gynaecologic surgical procedures and punch biopsies from the periurethral tissue were obtained. Immunohistochemistry for collagen type I, fibromodulin and lumican was performed on the histological slides. Results: In premenopausal incontinents the immunoreactivity for collagen type I was weaker with an irregular distribution compared to premenopausal controls; while for fibromodulin, the staining was stronger in premenopausal incontinents than in premenopausal controls. Between the two postmenopausal groups there was not a significant difference in the intensity of collagen type I and fibromodulin staining that instead were less strong than in premenopausal groups. Lumican staining had the same distribution in the four groups. Conclusions: Our results suggest an altered remodelling of connective tissue in the periurethral region of premenopausal patients with SUI, with a significant decrease of collagen content and an irregular organization and distribution of the collagen fibrils, compared to premenopausal controls. In the SUI patients this abnormal ECM remodelling, mainly related to the observed change in PGs expression, might affect significantly the tensile strength of the connective tissue and consequently the support that is provided by the urogenital suspensory apparatus to urethra and bladder base. Moreover, the significant decrease in collagen type I content in postmenopausal patients respect to premenopausal patients, suggests that age and hormonal factors could contribute to the pathological modifications of the supportive genitourinary connective tissues in the SUI patients. © 2007 Elsevier Ireland Ltd. All rights reserved.